Since the introduction of penicillin in the 1940s, the use of antibiotics has improved the expectancy and quality of life. Unfortunately however, the effectiveness of most antibiotics has declined due to the development of resistant microbial strains. A factor that has contributed to the development of such antibiotic resistant strains has been the chronic overuse of these drugs by the general population.
Recently, it has been recognized that natural antimicrobial peptides participate in the innate immune systems of animals and plants. Most of these antimicrobial peptides are cationic amphipathic molecules composed of 12 to 45 amino acid residues. These peptides act by permeabilizing the membrane forming pores and eventually cause cell lysis. It has been demonstrated that some of these peptides, as well as synthetic ones, exhibit activity against protozoan parasites (Jaynes et al., “In vitro cytocidal effect of novel lytic peptides on Plasmodium falciparum and Trypanosoma cruzi”, FASEB J., 2: 2878-2883 (1988); Arrowood et al., “In vitro activities of lytic peptides against the sporozoites of Cryptosporidium parvum”, Antimicrob. Agents Chemother, 35:224-227 (1991); Aley et al., “Killing of Giardia lamblia by cryptdins and cationic neutrophil peptides”, Infect. Immun. 62 (12): 5397-5403 (1994); Barr et al., “Activity of lytic peptides against intracellular Trypanossoma cruzi amastigotes in vitro and parasitemias in mice”, J. Parasitol., 81: 974-978 (1995), and; Martin et al., “Evaluation of the effect of peptidyl membrane-interactive molecules on avian coccidian”, Parasitol. Res., 85: 331-336(1999)). This mode of action endows antimicrobial peptides with broad activity against many bacteria, fungi and protozoa species. Unfortunately, heretofore naturally occurring antimicrobial peptides, e.g., indolicidin and tritrpticin, have had adverse effects on host cells susceptible to infection by the microorganisms (Hancock & Lehrer, “Cationic peptides: a new source of antibiotics”, Trends Biotech. 16: 82-88 (1998); Andreu & Rivas, “Animal antimicrobial peptides: An overview”, Peptide Science 47, 415-433 (1998)) and thus possess an inherent limitation as therapeutic agents. In addition, the effects of indolicidin and tritipticin are not universal and thus additional peptides with specificity for a broader range of pathogenic organisms or specificity for particular microorganisms are needed.
Accordingly, it is desirable to identify peptides that possess high specificity for pathogenic microorganisms, but have a low toxicity to host cells susceptible to infection by the pathogenic microorganisms. Such antimicrobial peptides would be useful for inhibiting infection, proliferation and viability of pathogenic microorganisms. It is also desirable to develop a method for assaying peptides for antimicrobial activity.